9064 RESULTS
COMMENT Endosomal trafficking dysfunction is a recognized pathogenic hub in Alzheimer’s disease. This elegant study provides further evidence for this, using two model systems, hiPSC-derived astrocytes and Baker’s yeast. Using isogenic APOE e3 and e4 human ...
COMMENT Narayan and colleagues integrate experiments in human astrocytes and yeast models to advance our understanding of endocytic perturbations in Alzheimer’s disease (AD). Based on human genome-wide association studies, a preponderance of AD candidate ...
COMMENT This paper elegantly combines two different techniques to discover that the AD risk gene PICALM modulates the AD-risk gene APOE4. The paper has a signature from two outstanding labs, combining yeast genetic assays (developed in the late Susan Lindquist’s ...
COMMENT Narayan et al. provide evidence of APOE4-induced perturbation to endocytosis in iPSC-derived astrocytes. This APOE4-mediated endocytic dysfunction results from a toxic gain of function of the APOE4 isoform and is cell-type-specific. They also performed ...
COMMENT Neuronal early endosome swelling and proliferation, among the earliest specific signs of AD, are linked to multiple downstream pathophysiological consequences (Nixon 2017; Pensalfini et al., 2020) and are driven by APP-dependent and-independent mechanisms ...
COMMENT This paper very interestingly reports APOE4-dependent endocytosis defects in astrocytes that can be rescued by CALM overexpression. The use of isogenic cultures of APOE4 astrocytes enabled the controlled analysis of endosomal Rabs, transferrin, and EGF ...
COMMENT This is a very nice study. It is the largest GWAS in African Americans so far, though it is far below the sample size of the genetic studies from Europeans, which included almost 100,000 individuals. This study suggests that it is possible additional ...
COMMENT This is a tour de force assessment of different antibodies previously reported to be specific for certain types of α-synuclein aggregate. They are not! I commend the authors for this thorough, systematic, honest, and self-critical approach to preparing ...
COMMENT The study from Kumar and colleagues is an important contribution to the field. It attempts to bring some consensus on the validity and characterization of these commonly used "conformation-specific" antibodies. Characterizing and validating ...
COMMENT Characterizing the transcriptomic changes of AD patient brains at the single-cell level enables the identification of cell-type-specific dysregulated pathways in AD. While single-nucleus RNA-sequencing (snRNA-Seq) allows examining the transcriptomic ...
COMMENT Few questions have led to more confusion than that of the relative importance of oligomers and filaments. Part of the problem stems from the fact that filaments are easily observed in human brain, whereas oligomers are largely invisible. It would ...
COMMENT Kumar and colleagues set out in their study to characterize a variety of available ‘conformation- specific antibodies’ for α-Syn to test the antibodies’ specificity toward monomeric, oligomeric and fibrillar forms of α-Syn. The results largely agree with ...
COMMENT In this important study, Kumar and colleagues conducted an impressive amount of rigorous work on the study of different forms and assemblies of alpha-synuclein, a central protein in synucleinopathies. The study is systematic, carefully executed, and ...
COMMENT I think most thoughtful people in the field have wished for better antibodies for some time. This work will make it clear how urgent that is. The question is whether it’s possible to get them. Structural biologists have often been suspicious of ...
COMMENT This is an extremely useful analysis of the current α-Syn antibodies used in the field, and quite an ‘eye-opener’. The study clearly shows that all the antibodies that have claimed to be ‘oligomer/conformation-specific’ also detect fibrils, i.e. the ...
